Genodermatoses and neurocutaneous skin findings — formative SAQs

Question 1 (10 marks, 15 minutes)

A four-year-old girl is referred because her teacher has noticed multiple flat brown patches on her skin and some difficulty with reading. On examination she has seven café-au-lait macules between six and twelve millimetres across, freckling in both axillae, and three small soft flesh-coloured nodules on the trunk. Her mother has a few café-au-lait macules and a facial plexiform swelling. Her blood pressure is normal. [1] [6]

(a) What is the most likely diagnosis and which diagnostic criteria confirm it? (4 marks)

The most likely diagnosis is neurofibromatosis type 1. The National Institutes of Health consensus criteria are met by two or more of the following, and this child has several: six or more café-au-lait macules of at least five millimetres before puberty, axillary freckling, two or more neurofibromas, and an affected first-degree relative (her mother). [1] [6]

(b) Outline the surveillance this child needs. (4 marks)

Surveillance is in a medical home and covers vision (at least annual assessment for the optic pathway glioma through the early school years, with dedicated imaging for any visual change or precocious puberty), blood pressure (annual, for renal artery stenosis and phaeochromocytoma), growth and puberty, skin and plexiform lesion assessment, and developmental, learning and behavioural surveillance. Routine brain imaging is not required in the asymptomatic child. [2] [6]

(c) What would prompt urgent referral of one of her skin lesions, and what diagnosis must be excluded? (2 marks)

A plexiform lesion that grows rapidly, becomes painful or firm, or produces a new neurological deficit must be referred urgently for imaging and biopsy to exclude a malignant peripheral nerve sheath tumour, because early recognition of this aggressive tumour changes the outcome. [2] [6]

Question 2 (10 marks, 15 minutes)

A six-month-old boy with known tuberous sclerosis complex, diagnosed after a cardiac rhabdomyoma in the newborn period, presents with clusters of sudden flexion spasms in series, each with a brief tonic stiffening. His mother thinks he has lost some social smiling. An electroencephalogram shows a hypsarrhythmic pattern. [4] [3]

(a) What is the seizure type and what is the first-line treatment? (3 marks)

The child has epileptic (infantile) spasms with hypsarrhythmia. Vigabatrin is the first-line agent for infantile spasms in tuberous sclerosis complex, started promptly once the diagnosis is confirmed, with ophthalmology surveillance for the irreversible visual-field toxicity that accompanies its use. [4] [3]

(b) What intracranial lesion requires surveillance in tuberous sclerosis, what complication does it cause, and how is the growing lesion treated? (4 marks)

The subependymal giant cell astrocytoma requires surveillance with magnetic resonance imaging at intervals, because as it grows near the foramen of Monro it can cause obstructive hydrocephalus and raised intracranial pressure. The growing lesion is treated with the mTOR inhibitor everolimus, which reduced lesion volume in the phase-three EXIST-1 trial and is now standard of care. [5] [3]

(c) Name four major diagnostic criteria for tuberous sclerosis complex. (3 marks)

Major criteria include three or more hypomelanotic macules, three or more angiofibromas or a fibrous cephalic plaque, the shagreen patch, cortical dysplasia or cortical tubers, subependymal nodules, the subependymal giant cell astrocytoma, cardiac rhabdomyoma, and renal angiomyolipoma. A definite clinical diagnosis needs two major or one major plus two minor criteria, or a pathogenic TSC1 or TSC2 variant. [4] [3]